Animal models are used for the evaluation of acellular pertussis vaccine components before use in clinical trials and administration to humans. The aerosol challenge model provides a reproducible system for the study of virulence factors in immunity involved in respiratory infection and subsequent disease. We are evaluating purified antigens of B. pertussis for their ability to protect neonatal mice against lethal respiratory infection. Active immunization with the B oligomer of pertussis toxin, as well as with a genetically engineered non-toxic mutant of pertussis toxin elicits specific antibody in the serum and lungs of mice and protects neonatal mice against lethal respiratory infection. Monoclonal antibodies directed against the lipooligosaccharide of B. pertussis outer membrane protein protects against leukocytosis and death, as well as decreased bacterial infection when passively administered. However, active immunization with the porin protein purified from B. pertussis was not found to protect, even though it was highly immunogenic. Studies are in progress to evaluate the protective ability and antigenicity of additional soluble and membrane-associated proteins .